Daxx shortens mitotic arrest caused by paclitaxel
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Updated: Jul 15, 2026
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Cory R Lindsay1, Axel Scholz, Viacheslav M Morozov
1Department of Anatomy and Cell Biology, and Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA.
Abstract:
Resistance to the anti-neoplastic drug paclitaxel is frequent in breast cancer patients. Most studies of paclitaxel resistance have focused on pathways that elicit cellular response, while little is known about players involved in the acquirement of taxane resistance. By screening a cohort of breast cancer cell lines, we observed a correlation between level of protein Daxx and response to paclitaxel. Cells lines expressing increased level of Daxx displayed a robust paclitaxel response with nearly all cells undergoing micronucleation, while cell lines with low amount of Daxx showed a decrease in micronucleation, and accumulation in mitosis. At used paclitaxel concentrations, apoptotic levels were negligible in all cell lines tested. Human cell lines expressing anti-Daxx siRNA as well as Daxx-/- mouse fibroblasts showed similar cellular response to paclitaxel. Importantly, absence or depletion of Daxx resulted in cell survival after paclitaxel treatment, as measured by colony formation assay. We conclude that Daxx may be an important predictive factor in cellular response to paclitaxel, which emphasizes a critical but unknown function of this protein in mitotic progression, which, when disabled, leads to survival advantages upon paclitaxel treatment.
Insights
Protein Daxx levels predict paclitaxel response in breast cancer. Low Daxx levels promote paclitaxel resistance by affecting mitotic progression, leading to cell survival.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Paclitaxel resistance is a significant challenge in breast cancer treatment.
- Current research on paclitaxel resistance primarily focuses on cellular response pathways, with limited understanding of resistance acquisition mechanisms.
- The role of protein Daxx in taxane resistance is largely unexplored.
Purpose of the Study:
- To investigate the correlation between protein Daxx levels and paclitaxel response in breast cancer.
- To elucidate the function of Daxx in mitotic progression and its impact on paclitaxel-induced cell death.
Main Methods:
- Screening of breast cancer cell lines for Daxx protein levels and paclitaxel response.
- Utilizing anti-Daxx siRNA in human cell lines and Daxx-/- mouse fibroblasts.
- Assessing cellular response through micronucleation, mitotic accumulation, apoptosis, and colony formation assays.
Main Results:
- A positive correlation was observed between high Daxx levels and robust paclitaxel response, indicated by increased micronucleation.
- Low Daxx levels were associated with decreased micronucleation, mitotic accumulation, and significantly enhanced cell survival after paclitaxel treatment.
- Apoptotic levels remained negligible across tested paclitaxel concentrations, irrespective of Daxx levels.
Conclusions:
- Protein Daxx may serve as a crucial predictive factor for paclitaxel response in breast cancer.
- Daxx plays a critical, previously unrecognized role in mitotic progression.
- Disruption of Daxx function confers a survival advantage upon paclitaxel treatment, highlighting a novel mechanism of taxane resistance.
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